Angiopoietin-like 4 protein (ANGPTL4) is a member of the angiopoietin family of secreted proteins. Conserved regions of the angiopoietin family include a coiled-coil domain and a C-terminal fibrinogen (FBN)-like domain. See, e.g., Kim et al., Biochem. J. 346:603-610 (2000). Other members of the family include angiopoietin 1, angiopoietin 2 and angiopoietin 3. Angiopoietin 1, angiopoietin 2 and angiopoietin 3/angiopoietin 4 bind to Tie2 receptor. See, e.g., Davis et al., Cell 87, 1161-1169 (1996); Maisonpierre et al., Science 277, 55-60 (1997); Valenzuela et al, Proc. Natl. Acad. Sci. USA 96, 1904-1909 (1999); and, U.S. Pat. Nos. 5,521,073; 5,650,490; and, 5,814,464. Angiopoietin 1 and 4 appear to be an agonist for the Tie2 receptor, while Angiopoietin 2 and 3 appear to be an antagonist (and possibly an agonist) for the Tie2 receptor. See, e.g., Folkman & D'Amore, Cell, 87:1153-1155 (1996); Suri et al., Cell, 87:1171-1180 (1996); Masionpierre et al., Science 277:55-60 (1997); and, Ward & Dumont, Seminars in Cell & Developmental Biology, 13:19-27 (2002). The Tie2 receptor belongs to a family of endothelial cell specific receptors tyrosine kinases, which also include the Tie1 orphan receptor. Another member of the family, angiopoietin-like 3 protein was found to bind to integrin αvβ3. See, e.g., US patent application 20030215451 and Camenisch et al., J. Biol. Chem., 277(19):17281-17290 (2002).
ANGPTL4 is known by other terms. For example, ANGPTL4 is also known as hepatic fibrinogen/angiopoietin-related protein (HFARP) (Kim et al., Biochem. J. 346:603-610 (2000)), PPARγ angiopoietin related protein (PGAR) (Yoon, et al., Mol. Cell Biol., 20:5343-5349 (2000)), and fasting induced adipose factor (FIAF) (Kerten et al., J. Biol. Chem., 275:28488-28493 (2000)).
In vitro and in vivo studies and characterizations of ANGPTL4 can provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with ANGPTL4 activity and/or expression. For example, tissue culture studies and genetically engineered mice have proven to be invaluable tools for the functional dissection of biological processes relevant to human disease, including immunology, cancer, neurobiology, cardiovascular biology, obesity and many others. There is a need to discover and understand the many biological functions of ANGPTL4. The invention addresses these and other needs, as will be apparent upon review of the following disclosure.